Objective:To investigate the level change of cytokines in patients with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:A retrospective case control study was conducted. The clinical data of 65 patients with EBV-HLH, 30 patients with infectious mononucleosis (IM) (IM group) and 40 patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis (non-EBV-HLH group) who admitted to Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from February 2022 to February 2023 were retrospectively analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of the interleukin (IL)-6, IL-2, IL-10, IL-8, IL-1β, tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in serum samples of patients in the above 3 groups. The cytokines levels in EBV-HLH group were compared with those in IM group and non-EBV-HLH group, respectively.Results:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α and IFN-γ in EBV-HLH group were higher than those in the non-EBV-HLH group, and the differences were statistically significant (all P < 0.05). The cytokines levels of IL-2, IL-10 and IFN-γ in EBV-HLH group were higher than those in IM group, and the differences were statistically significant (all P < 0.05). Conclusions:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α, IFN-γ are increased in EBV-HLH patients, which may play an important role in the development and progression of EBV-HLH.

Objective:To evaluate the diagnostic value of the von Willebrand factor (vWF) GPIb activity to antigen ratio for thrombotic thrombocytopenic purpura (TTP) at acute phase.Methods:A cohort of 93 patients with suspected TTP and admited to our hospitalfrom January 2018 to December 2019 were prospectively enrolled, we analyzed the levels of vWF: GPIb activity and vWF antigen at acute phase, the diagnosis of acquired TTP was defined as ADAMTS13 activity<10%.The PLASMIC score and final diagnosis of included patients were recorded.Results:Twenty-twopatients were diagnosed as TTP, the median (interquartile range) of ADAMTS13 activity were 1.0% (0-7.4%), other diagnoses included hemolytic uremic syndrome (HUS, n=8), severe infection ( n=21), malignancy( n=3), connective tissue disease( n=8), et al. The vWF: GPIb activity, vWF antigen, and ratio of vWF: GPIb activity to antigen were all significantly lower in patients with TTP than in those without ( P<0.05). The ratio of vWF: GPIb activity to vWF antigen <0.75 could yield a sensitivityof 81.8% and a specificity of 95.2% respectively for TTP. In patients with PLASMIC score≥6, 88.9% patients with the ratio of vWF: GPIb activity to vWF antigen <0.75 were confirmed as TTP, and 15.4% patients with the ratio≥0.75 were confirmed as TTP. Conclusions:The ratio of vWF: GPIb activity to vWF antigen based on automaticassays might be useful for differential diagnosis and stratification of TTP at acute phase, especially when the ADAMTS13 assay is not available in time.

Objective:To analyze the association of D-dimer levels, inflammatory indicators, cytokine abnormality, and disease severity in COVID-19 severe/critical type patients.Methods:The medical records of 41 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (28 patients) and critical type group (13 patients) . The levels of D-dimer, WBC, ANC, PCT, hsCRP, IL-2R, IL-6, IL-8, and TNF-α were compared among patients with different clinical types of COVID-19 infection. Moreover, the changes in the cytokines were analyzed in patients with different D-dimer levels. And, the levels of D-dimer, IL-2R, IL-6, IL-8, and TNF-α before and after anticoagulant therapy were assessed. Statistical analyses were performed using Student t test, Mann-Whitney U test, and Chi-square test. Results:Among the 41 patients, 23 were men (56.1%) and 18 were women (43.9%) ; the median patient age was 57 y. The age of the critical type patients [ (61.1±10.4) y] was higher than that of severe type patients [ (52.8±11.7) y]; the difference was significant ( t=-2.264, P=0.032) . The proportion of critical type patients with chronic diseases, especially hypertension, cardiovascular disease, and cerebrovascular disease, was higher as compared to that in those with severe type patients; the differences were significant (all P<0.05) . The prevalence of dyspnea, sweats, and fatigue symptoms in the critical type patients was higher than that in those with severe type disease; the differences were significant ( χ2=14.898, 6.972, 7.823; P<0.001, 0.008, 0.005) . The levels of D-dimer, WBC, ANC, PCT, hsCRP, and IL-8 in critical type patients were higher than those in severe type patients; the differences were significant (all P<0.05) . The levels of IL-2R, IL-8, and TNF-α in patients with abnormal D-dimer were higher as compared to those in patients with normal D-dimer levels; the differences were significant (all P<0.05) . Eight patients were treated with prophylactic anticoagulation; the levels of D-dimer, IL-2R, IL-6 and IL-8 after anticoagulant therapy were lower than those before treatment. Conclusions:COVID-19 critical type patients have more serious coagulation-immune dysfunction and dynamic monitoring of D-dimer and cytokines levels helps in identifying critical type patients as early as possible; anticoagulant therapy may improve the patient’s condition by correcting coagulation-immune dysfunction.

Autophagy plays an important dual role in the occurrence and development of acute leukemia, inducing the apoptosis of leukemia cells to suppress the development of acute leukemia, and protecting the leukemia cells to sustain the survival and to resist the apoptosis induced by chemotherapy drugs. Some studies have showed that the drug sensitivity of acute leukemia cells can be improved by regulating autophagy to induce the apoptosis of leukemia cells, and thus, regulating autophagy is expected to be an effective therapeutic strategy of refractory/relapsed acute leukemia. This article reviews the recent progress of autophagy and acute leukemia treatment.

Acute myeloid leukemia (AML) is considered to be an irreversible change of gene function caused by certain genetic changes, resulting in abnormal proliferation, differentiation disorder, and abnormal apoptosis of leukemia cells, leading to the occurrence and development of leukemia. Epigenetics refers to the change of heritable gene expression but the gene does not change in sequence. A large number of studies have shown that the pathogenesis of AML is closely related to the regulation of epigenetics. The regulation of epigenetic modification in the cellular metabolism, immune microenvironment and immune response of AML has been received increasing attention. This review will describe the regulation of epigenetics in the cellular metabolism, immune microenvironment and immune response of AML and the advances in the targeted intervention measures.

Objective To investigate the frequency of NPM1 mutation and its clinical significance in patients with cytogenetically normal acute myeloid leukemia (CN-AML). Methods The data of 190 patients with CN-AML were collected from Department of Hematology, Tongji Hospital between January 2008 and June 2015, and the discrepancies in clinical features and efficacy between CN-AML patients with NPM1 mutation and those without NPM1 mutation were also analyzed. Results Among the 190 CN-AML patients, NPM1 mutation was found in 44 patients (23.16 %). The proportion of bone marrow blast cells and the count of peripheral white blood cells in patients with NPM1 mutation were higher than those in patients without NPM1 mutation (75.82 % vs. 63.87 % , P <0.05; 75.7 ×109/L vs. 60.0 ×109/L, P <0.05). The rate of response (complete remission + partial remission) in patients with NPM1 mutation was also higher than that in patients without NPM1 mutation [70.09 %(22/31) vs. 56.91 %(45/79), P<0.05) ]. Conclusion NPM1 mutation is associated with higher tumor burden and higher remission rate in CN-AML patients.

Objective To analyze clinical and genetic risk factors of refractory or relapsed acute myeloid leukemia (AML) patients,and evaluate the efficacy of reinduction of chemotherapy.Methods 296 newly diagnosed AML patients,including 89 refractory or relapsed cases,were observed with clinical characteristics.And the efficiency of different reinduction chemotherapy regimens were compared.Results Compared with the non-refractory or relapsed AML,age,complex karyotype and Fms like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) gene mutations were risk factors of relapsed or refractory AML (P ＜ 0.05).Seventy-eight refractory and relapsed AML patients received reinduction therapy.The overall response rate (the complete response rate and the partial response rate) was 44.90 ％ (30/78).All reinduction regimens were divided into three categories:using the initial induction scheme or using new induction scheme including some chemotherapeutics without cross-resistance (regimen A),using the induction regimen containing medium-or high-dose cytarabine (regimen B),and using priming regimen containing of G-CSF,cytarabine,aclacinomycin or homoharringtonine (regimen C).Their overall response rate were 35.12 ％ (13/37),61.90 ％ (13/21) and 45.00 ％ (9/20),respectively,in which the overall response rate of regimen B was statistically higher than regimen A (P ＜ 0.05).Conclusions Age,complex karyotype and FLT3-ITD mutation were important causes of relapsed or refractory AML.The overall response rates were different among three different reinduction regimens.It is helpful to improve the overall response rate of reinduction therapy to use the regimen containing medium-or high-dose cytarabine,which was more suitable for young patients.For patients with poor tolerance,the priming regimen suit was more helpful to improve the overall response rate.

The effects of a novel immunosuppressive agent FTY720 on proliferation inhibition and apoptosis of acute leukemia cell lines HL-60 and U937, and the role of extracelluar regulated protein kinase (ERK) in the course of proliferation inhibition and apoptosis induced by FTY720 were studied. The proliferation inhibition rate of HL-60 and U937 cells by various concentrations of FTY720 was detected by MTT assay. Cell apoptosis was detected by DNA fragment analysis and flow cytometry. The phosphorylated ERK1/2 protein expression was observed by Western blotting. The change of intracellular distribution of ERK1/2 protein was identified by SP immunohistochemical staining. The results showed that FTY720 could inhibit the growth of HL-60 and U937 cells effectively in a dose-dependent manner. After incubation with FTY720 for 24 h, apoptosis was observed in HL-60 and U937 cells. The intracellular expression of phosphorylated ERK1/2 protein was also down-regulated and the distribution of ERK1/2 protein in cell nuclear was reduced during FTY720-induced apoptosis. So, that FTY720 inhibited ERK1/2 phosphorylation might mediate the role of FTY720-induced apoptosis and proliferation inhibition of leukemia cells.
Apoptosis ; drug effects ; Cell Division ; drug effects ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Fingolimod Hydrochloride ; HL-60 Cells ; Humans ; Immunosuppressive Agents ; pharmacology ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Propylene Glycols ; pharmacology ; Signal Transduction ; Sphingosine ; analogs & derivatives ; U937 Cells

To evaluate the therapeutic effect of hematopoietic stem cell transplantation (HSCT), we performed HSCT in 30 patients with hematologic maligancies. Of the 30 patients, 10 underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), 13 underwent myeloablative allogeneic HSCT while 7 underwent nonmyeloablative allogeneic HSCT, which were designated as autologous group, myeloablative group and nonmyeloablative group, respectively. All patients except the one who underwent cord blood transplantation, were successfully engrafted. Median time for the granulocytes > or = 0.5 x 10(9)/L and platelets > or = 20 x 10(9)/L were 12 days and 13 days respectively in autologous group, 16 days and 19 days in myeloablative group, 15 days and 12 days in nonmyeloablative group. In myeloablative group, acute graft-versus-host diseases (aGVHD) was observed in 3 patients, all of which were I-II grade. Oral mucous cGVHD was observed in 1 patient. In nonmyeloablative group, 1 patient developed intestinal aGVHD grade IV and cutaneous cGVHD was induced by donor lymphocyte infusions (DLI) in 3 patients. 1 patient had hematological relapse in autologous group. 1 patient had cytogenetic relapse in myeloablative group. In nonmyeloablative group 3 patients had cytogenetic relapse and were cured by DLI, 1 patient had hematological relapse. 4 of the 30 patients died of infection (2 patients), grade IV aGVHD (1) and relapse (1) respectively. 26 patients are still alive. 3 years overall survival (OS) and 3 years disease free survival (DFS) were 100% and 64.81% respectively in autologous group, 78.75% and 63% respectively in myeloablative group while both 66.67% in nonmyeloablative group. In conclusion, autologous group had less transplant-related complications and mortality. Active prophylaxis of relapse could significantly promote DFS. The transplant-related mortality limited DFS in myeloablative group. More relapses occurred in nonmyeloablative group, but could be cured by DLI.
Adolescent ; Adult ; China ; epidemiology ; Female ; Follow-Up Studies ; Graft vs Host Disease ; epidemiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Leukemia ; surgery ; Leukemia, Myeloid, Acute ; surgery ; Leukemia, Myelomonocytic, Chronic ; surgery ; Lymphoma ; surgery ; Male ; Middle Aged

To evaluate the therapeutic effect of hematopoietic stem cell transplantation (HSCT), we performed HSCT in 30 patients with hematologic maligancies. Of the 30 patients, 10 underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), 13 underwent myeloablative allogeneic HSCT while 7 underwent nonmyeloablative allogeneic HSCT, which were designated as autologous group, myeloablative group and nonmyeloablative group, respectively. All patients except the one who underwent cord blood transplantation, were successfully engrafted. Median time for the granulocytes > or = 0.5 x 10(9)/L and platelets > or = 20 x 10(9)/L were 12 days and 13 days respectively in autologous group, 16 days and 19 days in myeloablative group, 15 days and 12 days in nonmyeloablative group. In myeloablative group, acute graft-versus-host diseases (aGVHD) was observed in 3 patients, all of which were I-II grade. Oral mucous cGVHD was observed in 1 patient. In nonmyeloablative group, 1 patient developed intestinal aGVHD grade IV and cutaneous cGVHD was induced by donor lymphocyte infusions (DLI) in 3 patients. 1 patient had hematological relapse in autologous group. 1 patient had cytogenetic relapse in myeloablative group. In nonmyeloablative group 3 patients had cytogenetic relapse and were cured by DLI, 1 patient had hematological relapse. 4 of the 30 patients died of infection (2 patients), grade IV aGVHD (1) and relapse (1) respectively. 26 patients are still alive. 3 years overall survival (OS) and 3 years disease free survival (DFS) were 100% and 64.81% respectively in autologous group, 78.75% and 63% respectively in myeloablative group while both 66.67% in nonmyeloablative group. In conclusion, autologous group had less transplant-related complications and mortality. Active prophylaxis of relapse could significantly promote DFS. The transplant-related mortality limited DFS in myeloablative group. More relapses occurred in nonmyeloablative group, but could be cured by DLI.
China/epidemiology ; Follow-Up Studies ; Graft vs Host Disease/*epidemiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Leukemia/*surgery ; Leukemia, Myelomonocytic, Chronic/surgery ; Leukemia, Nonlymphocytic, Acute/surgery ; Lymphoma/surgery